James Waxmonsky, MD

Asthma is one of the most impairing diseases of childhood, affecting more than 6% of children.

 Each year, it is responsible for 14 million lost school days and $3 billion in treatment costs.

 The earliest definitions of asthma recognized the impact of psychological distress on the disorder. While most would agree that having a chronic illness increases the risk of depression, there is emerging evidence that depression may have an impact on the onset and course of asthma. Several mechanisms have been suggested as explanations for the association between the 2 disorders. Many of these models focus on the impact of depression on treatment adherence and risk-taking behaviors in adolescence (eg, smoking, binge drinking), which alter asthma control; however, studies have found that adherence models cannot explain all the effects of depression on asthma.

Recent research found that compared with euthymic adults, depressed adults have reduced knowledge of their asthma and ability to identify the signs of worsening asthma.

 These findings suggest that depression may also impair asthma control by reducing a person's ability to identify symptom exacerbations in a timely fashion. Direct psychobiologic pathways among stress, emotions, and asthma severity have also been hypothesized. For example, it is thought that early psychosocial distress may affect the development of the immune system, thereby affecting the onset of asthma.

 However, this theory is more relevant to stressors during infancy than to the effects of depression later in childhood. In this regard, Miller and Wood

 have proposed that the autonomic dysregulation seen in depressed emotional states may potentiate vagally mediated asthma exacerbations.

The combination of depression and asthma has been associated with increased morbidity and mortality in adults and children.

 In a double-blind, placebo-controlled study, an improvement in depressive symptoms in asthmatic adults was associated with a reduction in asthma severity and frequency of corticosteroid use.

 While controlled treatment studies of depression have not been completed in asthmatic children, the efficacy of psychosocial interventions for stress reduction in this population has been evaluated.

 Biofeedback, cognitive-behavioral therapy, and progressive relaxation have been found to improve outcome, although there are few controlled efficacy studies. There is an increasing effort to screen for depression in children with asthma, since the identification of treatable comorbid conditions that worsen asthma severity may improve the long-term course of the disorder.

Up to 50% of adults with asthma will experience depression in their lifetime.

 Children with asthma also have increased rates of depression and anxiety,

 although findings vary across studies with regard to the exact prevalence of depression and the impact of mood symptoms on asthma severity. These discrepancies probably stem from the different measures used to assess depressive symptoms, with few studies integrating both child and parent reports with direct clinical observation. Many studies relied solely on the parent-report form of the Child Behavior Checklist (CBCL), which was designed to assess global functioning, not depression. Parents' ratings of their child's mood could be impacted by their own depression,

 and there is concern that parents of medically ill children may be hypervigilant about signs of depression in their child, limiting the reliability of parent reports.

Child self-report measures should not be affected by biases in parent reporting. To date, children's self-reports of depressive symptoms have been assessed primarily using the Children's Depression Inventory (CDI), which, unlike the CBCL, inquires about symptoms specific to pediatric depression. While the psychometrics of this scale have been well established in medically healthy populations, it has not been extensively validated in children with chronic medical illnesses. Moreover, in pediatric depression trials, young children tended to underreport depressive symptoms, compared with parents and clinicians.

 In asthma studies, children's reports of internalizing psychopathology correlated poorly with asthma severity.

Clinician-driven ratings of depression would avoid the potential confounding factor of parent mood and are generally deemed more reliable than the child's report of his or her mood. However, these ratings have not been widely used in pediatric asthma studies. When implemented, most studies have used structured interviews, such as the Diagnostic Interview Schedule for Children, which do not require experienced raters who can integrate symptom reports with direct observation of the child. Many structured interviews rely on categorical definitions of depressive symptoms (either present or not) that do not adequately identify subthreshold depressive states and that have limited statistical power to detect correlations. Given these limitations, it is not surprising that several studies have failed to find a relationship between asthma severity and depressive symptoms.

The Children's Depression Rating Scale-Revised (CDRS-R) has become the standard assessment tool for depression in pediatric antidepressant trials, including the much-publicized Treatment for Adolescents With Depression Study.

 In this scale, trained raters integrate information from direct observation, child report, and parent report into one composite score of depressive symptoms.

 The scale, which is modeled after the Hamilton Rating Scale for Depression in adults, yields a total score of 17 to 113; a score of 40 or above is considered to be a strong indicator of an impairing depressive state and a score of 30 or above indicates the presence of subthreshold depressive symptoms.

The CDRS-R has been shown to reliably detect meaningful depressive states in normal and psychiatric populations.

 Although it does require trained raters to administer reliably, it is less time-consuming than most structured interviews and provides a dimensional measure of depressive symptoms. Moreover, there do not appear to be problems with parent overreporting in nonpsychiatric samples.

 In a psychiatric setting where trained raters are available, the CDRS-R appears to be an excellent choice for assessing depressive symptoms in children with asthma, but it has not been well studied in this population.

We recently published a study using the CBCL, CDI, and CDRS-R to identify the prevalence of depressive symptoms in asthmatic children from a primarily inner-city population (74% with moderate to severe asthma) and assess the correlation of these symptoms with asthma severity.

 Given the potential confound of parent mood, we also assessed depression in parents using the Beck Depression Inventory (BDI). The unique aspects of this study were the use of depression scales from 3 different raters (parent, child, and clinician); the use of the CDRS-R in an asthmatic sample; and defining asthma severity based on National Heart, Lung, and Blood Institute criteria, which integrate parent and child reports of asthma symptoms with forced expiratory volume in 1 second (FEV

) scores. It was hypothesized that there would be an elevated rate of depressive symptoms, with the CDRS-R score producing the best correlation with asthma severity, since it integrates parent and child reports with direct clinical observation.	

One quarter of the 129 children scored in the clinical range (defined as a T-score of greater than 65 for all scales to equilibrate findings across measures) on any single depression scale (21% on the CBCL, 5% on the CDI, and 6% on the CDRS-R), but only 3% scored in the clinical range on all measures. Of the patients identified as depressed on at least 1 scale, 30% scored in the clinical range on 2 scales, with the best agreement between CDRS-R and CDI (21%) and between CBCL and CDRS-R (21%). Compared with standardized norms, mean scores for the sample were elevated on the CDRS-R (32) and CBCL (T-score of 58 on the internalizing subscale) but not on the CDI (8.5). Hence, there was an elevated rate of depressive symptoms that were primarily driven by parent report.

 Among the mothers, 43% scored in the depression range with a mean score of 11.3, which is above the standard cutoff for depression (10). Correlation between informants was low. Interestingly, the CDRS-R did not identify more depressed patients than did the CDI, and the 2 scales largely identified different patients as depressed. Most identified cases of depression have not yet been clinically confirmed, which allows for the determination of which scale is the optimal tool for evaluating depression in children with asthma.

Surprisingly, the CDI score was most strongly correlated with asthma severity (

 < .01). While the effect size was small (6% to 7% of the variance in asthma severity was attributable to CDI score), it was consistent with the results of other studies examining the effects of psychological variables on asthma severity.

 The CDRS-R failed to correlate with asthma severity even after controlling for age, sex, and parent depression. Because asthma severity was defined by integrating objective medical indices with child and parent reports, it is unlikely that these correlations were inflated by reporter bias from a somatically oriented informant (ie, a parent or child who reports elevated mood symptoms is more likely to report asthma symptoms).

Nonetheless, because of the high rates of parent depression and the correlation between parent and child depressive symptoms (

 < .05), the effect of maternal depression was factored out to remove any potential bias of mood on parent reporting. There was no significant change in the associations between asthma severity and any of the parent-reported depression measures after factoring out maternal depression.

 found that inducing feelings of sadness and despair in a laboratory setting produced changes in oxygen saturation that were consistent with airway constriction. In nonpsychiatric samples, children are more likely to report depressive thoughts or feelings, while parents are more likely to report behavior changes.

 A recent factor analysis of the CDRS-R also found limited correlation between clinician ratings of observed affect and a child's report of his internal mood state.

 These findings suggest that observable signs of depression, such as changes in sleep, appetite, or frustration tolerance, may not be directly related to physiologic parameters relevant to asthma. Self-report forms may more accurately capture the depressive symptoms that are physiologically germane to asthma, such as internal mood state, which should be the target of depression treatments in children with asthma.

The cross-sectional nature of these findings does not allow for a determination of the causal pathways between depression and asthma. While it seems likely that the interaction is bidirectional, it is unknown whether depression primarily drives asthma severity or the reverse. Psychosocial adversity or treatment adherence could also explain the association between depression and asthma severity. However, the specific connection between self-reported depressive symptoms and asthma severity that was unaffected by parent mood is suggestive of a direct link between the two. We are currently running a laboratory protocol to identify the pathways and mechanisms by which depressed mood produces airway compromise in asthma.

These findings suggest that treatment of depression may improve asthma outcomes in comorbidly ill children. We are in the process of designing an intervention trial for depressed adolescents with asthma to further evaluate this possibility.

Our group provides clinical treatment to a large number of children with asthma and psychiatric illnesses and has found that depression can be safely and effectively treated in the presence of asthma. There are few drug-drug interactions between the SSRIs and asthma medications, although paroxetine and fluoxetine should be used cautiously with other drugs that are metabolized through the cytochrome P-450 2D6 hepatic pathways. ß-Blockers are contradicted in patients with asthma and oral steroids may exacerbate mood symptoms in children with preexisting psychiatric illness, necessitating careful monitoring when prescribed. As with any child or adolescent, FDA warnings regarding the use of antidepressants in children younger than 18 years should be reviewed with the family before prescribing, and careful monitoring for adverse emotional reactions is recommended.

There is an elevated rate of depression in children and adults with asthma that appears to be associated with worsening asthma severity. Self-reported depressive symptoms may be of particular concern in asthmatic children. Therefore, any attempt to assess depression should include a direct interview with the child, and the CDI appears to be a useful tool for this purpose. While there are few data on the treatment of depression in children who have asthma, clinical experience suggests that in most cases they may be safely and effectively treated with existing depression treatments, including SSRIs. While initial reports are encouraging, controlled studies are needed to see whether improvement in mood leads to enhanced medical outcomes.

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Articles

Asthma is one of the most impairing diseases of childhood, affecting more than 6% of children. Each year, it is responsible for 14 million lost school days and $3 billion in treatment costs.

James Waxmonsky, MD

Articles

The Assessment and Management of Depression in Children With Asthma